氯化血红素催化重氮化合物经由卡宾中间体的反应研究

发布时间：2018-04-17 12:43

本文选题：重氮化合物 + 金属卡宾　；参考：《浙江大学》2017年博士论文

【摘要】：血红素是自然界中含量最为丰富的天然铁卟啉复合物,存在于多种血红素蛋白中,承担着重要的催化活性。近几十年,以其为活性辅基的血红素蛋白如肌红蛋白、辣根过氧化物酶、细胞色素P450等被广泛用于各种生物化学研究中,而血红素自身却很少被用于催化有机反应,尤其是非天然化学反应。另一方面,以重氮化合物为前体的金属卡宾是近些年的研究热点,它可以与亲核试剂发生不同的转化反应,如X-H插入反应(X=N,S,O,C,Si,B...)、环丙烷化反应和叶立德形成反应等,在有机合成中有着重要的作用。本论文主要围绕氯化血红素在非天然卡宾化学中的催化作用展开,研究结果主要包括以下三个方面:水相中氯化血红素-环糊精体系催化的N-H键插入反应:建立了氯化血红素-环糊精水相催化体系,实现了水溶液中的αα-重氮酯与芳香胺类化合物的N-H键插入反应,含多种取代基的苯胺、萘胺、四氢吲哚都适用于该反应,产率最高可达96%。另外,通过调控环糊精腔体大小可以一定程度上调节苯胺与重氮乙酸乙酯的单N-H键插入产物和双N-H键插入产物的比例。水相中氯化血红素-环糊精-曲拉通X-100体系催化的硫叶立德的形成及其Doyle-Kirmse反应:通过在之前的氯化血红素-环糊精体系中引入表面活性剂曲拉通X-100,实现了氯化血红素在水相中催化重氮化合物和烯丙基硫醚产生硫叶立德,并进一步发生Doyle-Kirmse重排反应。该催化体系反应条件温和,具有优良的底物普适性和良好的反应产率,对非水溶性的芳基烯丙基硫醚或烷基烯丙基硫醚都适用。氯化血红素催化的硫叶立德的形成及其底物控制的化学选择性的[1,2]-Stevens和Sommelet-Hauser重排反应:通过对苄基硫醚的苄基上取代基电子效应的控制和溶剂的选择,实现了经由血红素卡宾产生的苄基硫叶立德选择性地发生[1,2]-Stevens反应和Sommelet-Hauser重排反应,给电子基团或弱吸电子基团取代的苄基硫醚易发生[1,2]-Stevens反应,而对位强吸电子基团取代的苄基硫醚却更易于发生Sommelet-Hauser反应,且水溶液和适当降低温度可以促进Sommelet-Hauser反应。
[Abstract]:Heme is the most abundant natural iron porphyrin complex in nature. It exists in a variety of heme proteins and plays an important catalytic role.In recent decades, heme proteins, such as myoglobin, horseradish peroxidase, cytochrome P450 and so on, have been widely used in various biochemical studies, but heme itself is rarely used to catalyze organic reactions.Especially unnatural chemical reactions.On the other hand, metal carbene with diazo compounds as precursor has been a hot research topic in recent years. It can undergo different conversion reactions with nucleophilic reagents, such as X-H insertion reaction, X ~ (2 +) -N ~ (2 +) ~ (2 +) -C ~ (2 +) SiB..0.The reaction of cyclopropanation and ylide formation, etc.Play an important role in organic synthesis.This paper focuses on the catalytic role of hemin in unnatural carbene chemistry.The results mainly include the following three aspects: the N-H bond insertion reaction catalyzed by hemin cyclodextrin system in water phase: the water phase catalytic system of hemin cyclodextrin was established.The N-H bond insertion reaction of 伪伪 -diazoate with aromatic amines in aqueous solution was realized. Aniline, naphthylamine and tetrahydroindoles containing a variety of substituents were all suitable for the reaction, with the highest yield of 96.In addition, by regulating the size of cyclodextrin cavity, the ratio of aniline to diazoacetate N-H bond insertion product and double N-H bond insertion product can be adjusted to a certain extent.Formation of Sulphur and its Doyle-Kirmse reaction catalyzed by Hemin cyclodextrin-Traetone X-100 system in Aqueous Phase: blood Chloride was achieved by introducing Surfactant Traetone X-100 into the previous heme Cyclodextrin systemDiazo compounds and allyl sulfides are catalysed in aqueous phase by bilirubin to produce sulfurylides.Further Doyle-Kirmse rearrangement reaction occurred.The reaction conditions of the catalyst system are mild, with excellent substrate universality and good reaction yield. It is suitable for both aryl allyl sulfide and alkyl allyl sulfide which are insoluble.Heme-catalyzed [1z2] -Stevens and Sommelet-Hauser rearrangement of sulfoylides and their substrate-controlled chemical selectivity: through the control of the electron effect of substituents on benzyl sulfides and the selection of solvents,The benzyl thioylide produced by heme carbene has been selectively rearranged in [1t2] -Stevens reaction and Sommelet-Hauser rearrangement reaction. The [1t2] -Stevens reaction is easy to occur when the electron group or the benzyl sulfide substituted by the weak electron group is given.On the other hand, benzyl sulfides substituted by p-potential strong electron-absorbing groups are more likely to react with Sommelet-Hauser, and the Sommelet-Hauser reaction can be promoted by aqueous solution and proper lowering of temperature.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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